PROJECT SUMMARY AND ABSTRACT BU-CMD Chemical Library Consortium: Fostering Collaborations between Chemists and Biologists for Translational Discovery Small molecules are powerful tools for understanding biological systems, and form the foundation for most therapies of human disease. The successful translation of a bioactive small molecule into a safe, effective therapeutic requires the collective involvement of both chemists and biologists. The Boston University Center for Molecular Discovery (BU-CMD) is a laboratory that connects chemists who make molecules with biologists who wish to test them in various diseases. The BU-CMD serves as a collaborative nexus that bridges these connections, seeding new discoveries and providing the critical chemistry support required to further develop existing leads. The objective of this program is to leverage existing BU-CMD resources across multiple CTSA hubs, establishing an expandable molecule distribution infrastructure for seeding and fostering collaborative research projects between chemists and translational scientists. The overarching goal of the project is to advance curative research for challenging biological disease areas. The BU-CMD has longstanding experience in curating and openly distributing a small molecule screening collection of diverse, structurally complex chemotypes, through a unique, homegrown consortium of biological screeners called the Chemical Library Consortium (CLC). The CLC has been unique in its ability to enable new discoveries and foster meaningful collaborative follow-up on these discoveries toward translational drug discovery. This proposal describes the formal connection of the CLC with the CTSA through the establishment of an open access, CTSA-based compound sharing network centered at Boston University. The proposed U01 program will curate molecules from synthetic organic chemists at six CTSA hubs (Boston University, New York University, University of North Carolina, Chapel Hill, University of California Los Angeles, The University of Chicago, and University of Notre Dame) and will distribute them within the CLC network. The CLC network will be expanded as part of this grant to include new translational scientists at the Vanderbilt University and University of Massachusetts Medical School hubs. Lastly, a formal connection will be forged between the BU-CMD and NCATS in order to connect translational scientists to resources and technologies developed herein. This consortium aims to connect scientific resources across CTSA hubs, and seed new collaborations between translational scientists at these hubs, and improve upon existing infrastructure for the discovery and progression of small molecule therapies for diseases.